NCT03772288

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD) and/or recommended phase 2 dose (RP2D) for TAK-659 when administered in combination with NKTR-214.

Trial Health

33
At Risk

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Trial has exceeded expected completion date
Timeline
Completed

Started Apr 2019

Typical duration for phase_1

Geographic Reach
2 countries

6 active sites

Status
withdrawn

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

December 10, 2018

Completed
1 day until next milestone

First Posted

Study publicly available on registry

December 11, 2018

Completed
4 months until next milestone

Study Start

First participant enrolled

April 3, 2019

Completed
2.6 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

November 10, 2021

Completed
7 days until next milestone

Study Completion

Last participant's last visit for all outcomes

November 17, 2021

Completed
Last Updated

February 8, 2023

Status Verified

February 1, 2023

Enrollment Period

2.6 years

First QC Date

December 10, 2018

Last Update Submit

February 6, 2023

Conditions

Keywords

Drug Therapy

Outcome Measures

Primary Outcomes (2)

  • MTD of TAK-659 in Combination with NKTR-214

    3 weeks after last dose of last participant in dose escalation or up to 6 months

  • RP2D of TAK-659 in Combination with NKTR-214

    3 weeks after last dose of last participant in dose escalation or up to 6 months

Secondary Outcomes (9)

  • Cmax: Maximum Observed Plasma Concentration for TAK-659

    Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)

  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for TAK-659

    Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)

  • AUCτ: Area Under the Plasma Concentration-time Curve From Time During the Dosing Interval for TAK-659

    Cycle 1 and Cycle 2: Day 1 pre-dose and at multiple time points (up to 24 hours) post-dose (cycle length=21 days)

  • Cmax: Maximum Observed Plasma Concentration for NKTR-214

    Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)

  • Tmax: Time to Reach the Maximum Plasma Concentration (Cmax) for NKTR-214

    Cycle 1 Day 1 pre-dose and at multiple time points (up to 168 hours) post-dose (cycle length=21 days)

  • +4 more secondary outcomes

Study Arms (2)

Dose Escalation: TAK-659 + NKTR-214

EXPERIMENTAL

TAK-659 tablet, orally, once daily along with NKTR-214, infusion, intravenously, once on Day 1 in a 21-day treatment cycle, until disease progression, unacceptable toxicities, or discontinuation by participant. The dose escalation phase will determine the MTD or RP2D of TAK-659. Dose escalation of TAK-659 will be based on available safety and tolerability data.

Drug: TAK-659Drug: NKTR-214

Safety Expansion: TAK-659 + NKTR-214

EXPERIMENTAL

TAK-659, tablet, orally, once daily along with NKTR-214, infusion, intravenously, once on Day 1 of 21-day treatment cycle, until disease progression, unacceptable toxicities, or discontinuation by participants. TAK-659 and NKTR-214 MTD/RP2D will be determined from the dose escalation phase.

Drug: TAK-659Drug: NKTR-214

Interventions

Tablets.

Dose Escalation: TAK-659 + NKTR-214Safety Expansion: TAK-659 + NKTR-214

Intravenous infusion.

Dose Escalation: TAK-659 + NKTR-214Safety Expansion: TAK-659 + NKTR-214

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Histologically or cytologically confirmed diagnosis of advanced B-cell NHL, including diffuse large B-cell lymphoma (DLBCL), follicular lymphoma (FL), marginal zone lymphoma (MZL), or mantle cell lymphoma (MCL) (Waldenstrom macroglobulinemia \[WM\] and chronic lymphocytic leukemia \[CLL\]/small lymphocytic leukemia \[SLL\] are excluded).
  • Radiographically or clinically measurable disease with at least 1 target lesion per (greater than \[\>\] 1.5 centimeter \[cm\] in the longest diameter for a lymph node or nodal mass, or \>1.0 cm in the longest diameter for extranodal disease) Lugano 2014 criteria for malignant lymphoma.

You may not qualify if:

  • Eastern Cooperative Oncology Group (ECOG) performance status score of 0 or 1 and life expectancy of \>3 months.
  • Must have adequate organ function.
  • Recovered (that is, less than or equal to \[\<=\] Grade 1 toxicity) from the clinically significant reversible effects of prior anticancer therapy.
  • Central nervous system (CNS) lymphoma; active brain or leptomeningeal metastases, as indicated by positive cytology from lumbar puncture or computed tomography (CT) scan/magnetic resonance imaging. Exceptions include those participants who have completed definitive therapy, are not on steroids, have a stable neurologic status for at least 2 weeks after completion of the definitive therapy and steroids, and do not have neurologic dysfunction that would confound the evaluation of neurologic and other AEs.
  • Known human immunodeficiency virus (HIV) infection or HIV-related malignancy, hepatitis B surface antigen positive, or known or suspected active hepatitis C infection.
  • History of drug-induced pneumonitis requiring treatment with steroids; history of idiopathic pulmonary fibrosis, organizing pneumonia, or evidence of active pneumonitis on screening chest CT scan; history of radiation pneumonitis in the radiation field (fibrosis) is permitted.
  • Systemic anticancer treatment (including investigational agents) or radiotherapy less than 2 weeks before the first dose of study treatment (\<=4 weeks for antibody-based therapy including unconjugated antibody, antibody-drug conjugate, and bi-specific T-cell engager agents; \<=8 weeks for cell-based therapy or antitumor vaccine).
  • Participants in need of immediate cytoreductive therapy.
  • Prior autologous stem cell transplant (ASCT) within 6 months or prior ASCT at any time without full hematopoietic recovery, defined by the entry criteria in the study, before Cycle 1 Day 1 or allogeneic stem cell transplant any time.
  • Use or consumption of:
  • Medications or supplements that are known to be inhibitors of P-glycoprotein (P-gp) and/or strong reversible inhibitors of cytochrome (CYP3A), strong CYP3A mechanism-based inhibitors, strong CYP3A inducers or P-gp inducers within 5 times the inhibitor half-life or within 7 days before the first dose of study drug. In general, the use of these agents is not permitted during the study except in cases in which an AE must be managed.
  • Grapefruit-containing food or beverages within 5 days before the first dose of study drug. Note that grapefruit-containing food and beverages are not permitted during the study.
  • Active, known, or suspected autoimmune disease. Participants requiring systemic treatment within the past 3 months or with a documented history of clinically severe autoimmune disease that requires systemic steroids or immunosuppressive agents. (Exceptions include any patient taking 10 mg or less of prednisone or equivalent, participants with vitiligo, hypothyroidism stable on hormone replacement, type 1 diabetes, Graves disease, Hashimoto disease, alopecia areata, eczema, or with medical monitor approval.)
  • History of organ or tissue transplant that requires systemic use of immunosuppressive agents.
  • Prior treatment with TAK-659 or any spleen tyrosine kinase (SYK) inhibitor or interleukin-2 (IL-2) therapy.
  • +4 more criteria

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (6)

University of Alabama at Birmingham

Birmingham, Alabama, 35294, United States

Location

Henry Ford Hospital

Detroit, Michigan, 48202, United States

Location

New York University Langone Medical Center

New York, New York, 10016, United States

Location

Alberta Health Services

Calgary, Alberta, T2N 2T9, Canada

Location

Jewish General Hospital

Montreal, Quebec, H3T1E2, Canada

Location

Centre Hospitalier Universitaire de Sherbrooke (CIUSSS de lEstrie - CHUS)

Sherbrooke, Quebec, J1H 5N3, Canada

Location

MeSH Terms

Conditions

Lymphoma, Non-Hodgkin

Interventions

TAK-659bempegaldesleukin

Condition Hierarchy (Ancestors)

LymphomaNeoplasms by Histologic TypeNeoplasmsLymphoproliferative DisordersLymphatic DiseasesHemic and Lymphatic DiseasesImmunoproliferative DisordersImmune System Diseases

Study Officials

  • Medical Director

    Millennium Pharmaceuticals, Inc.

    STUDY DIRECTOR
0

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
SEQUENTIAL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

December 10, 2018

First Posted

December 11, 2018

Study Start

April 3, 2019

Primary Completion

November 10, 2021

Study Completion

November 17, 2021

Last Updated

February 8, 2023

Record last verified: 2023-02

Data Sharing

IPD Sharing
Will share

Takeda makes patient-level, de-identified data sets and associated documents available after applicable marketing approvals and commercial availability have been received, an opportunity for the primary publication of the research has been allowed, and other criteria have been met as set forth in Takeda's Data Sharing Policy (see www.TakedaClinicalTrials.com/Approach for details). To obtain access, researchers must submit a legitimate academic research proposal for adjudication by an independent review panel, who will review the scientific merit of the research and the requestor's qualifications and conflict of interest that can result in potential bias. Once approved, qualified researchers who sign a data sharing agreement are provided access to these data in a secure research environment.

Locations